The molecular biology and hematological laboratory support to all units of the Center. Besides standard hematological and biochemical testings, it offers, by DNA analysis, precise genetic classification of all patients. The number of S genes and alpha-globin genes are enumerated and the haplotypes of the beta-globin like gene cluster are determined to define with precision the genotype of the patients. A battery of hematological parameters, including the levels of adhesion molecules reflecting endothelial damage, will be measured. These will be correlated with clinical manifestations by the statistical core unit to derive prognostic factors. This unit provides prenatal diagnosis of sickle cell diseases to all who request it. This is the largest program of prenatal diagnosis of sickle cell disease in the world. This unit will sharpen diagnostic techniques for prenatal diagnosis, such as the use of allele-specific PCR for fast diagnosis and the analysis of the Variable Number of Tandem Repeats (VNTR) to ascertain the contamination by maternal cells of chorionic villi samples. A major undertaking of this unit will be the development of techniques to obtain the prenatal diagnosis from a sample of maternal blood. This study, in cooperation with Dr. D.Bianchi at the New England Medical Center, will utilize analysis of fetal normoblasts circulating in the maternal blood. Nucleated red cells will be first concentrated by our technique of ultri- centrifugation on discontinuous gradients of arabino-galactane. Fetal cells will then be isolated by fluorescent activated sorting, using fluorescein-conjugated antibodies to cytoplasmic gamma-globin. The diagnosis will be made by PCR and the origin of the cells verified by analysis of Y-linked genes and/or by the VNTR analysis.